Hoxmeier J Charles, Thompson Brice D, Broeckling Corey D, Small Pamela, Foy Brian D, Prenni Jessica, Dobos Karen M
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523.
Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO 80523.
Sci Rep. 2015 Mar 18;5:9242. doi: 10.1038/srep09242.
Infection with Mycobacterium ulcerans causes Buruli Ulcer, a neglected tropical disease. Mosquito vectors are suspected to participate in the transmission and environmental maintenance of the bacterium. However, mechanisms and consequences of mosquito contamination by M. ulcerans are not well understood. We evaluated the metabolome of the Anopheles gambiae mosquito to profile the metabolic changes associated with bacterial colonization. Contamination of mosquitoes with live M. ulcerans bacilli results in disruptions to lipid metabolic pathways of the mosquito, specifically the utilization of glycerolipid molecules, an affect that was not observed in mosquitoes exposed to dead M. ulcerans. These results are consistent with aberrations of lipid metabolism described in other mycobacterial infections, implying global host-pathogen interactions shared across diverse saprophytic and pathogenic mycobacterial species. This study implicates features of the bacterium, such as the putative M. ulcerans encoded phospholipase enzyme, which promote virulence, survival, and active adaptation in concert with mosquito development, and provides significant groundwork for enhanced studies of the vector-pathogen interactions using metabolomics profiling. Lastly, metabolic and survival data suggest an interaction which is unlikely to contribute to transmission of M. ulcerans by A. gambiae and more likely to contribute to persistence of M. ulcerans in waters cohabitated by both organisms.
溃疡分枝杆菌感染会引发布氏杆菌病,这是一种被忽视的热带疾病。蚊子被怀疑参与了该细菌的传播和环境维持。然而,溃疡分枝杆菌对蚊子的污染机制及后果尚未得到充分了解。我们评估了冈比亚按蚊的代谢组,以描绘与细菌定殖相关的代谢变化。用活的溃疡分枝杆菌杆菌污染蚊子会导致蚊子脂质代谢途径的紊乱,特别是甘油脂质分子的利用,而在接触死的溃疡分枝杆菌的蚊子中未观察到这种影响。这些结果与其他分枝杆菌感染中描述的脂质代谢异常一致,这意味着不同腐生和致病分枝杆菌物种之间存在共同的宿主-病原体全局相互作用。这项研究揭示了该细菌的一些特征,例如假定的溃疡分枝杆菌编码的磷脂酶,它与蚊子发育协同促进毒力、生存和主动适应,并为使用代谢组学分析加强对媒介-病原体相互作用的研究提供了重要基础。最后,代谢和生存数据表明,这种相互作用不太可能促进冈比亚按蚊传播溃疡分枝杆菌,而更有可能促进溃疡分枝杆菌在两种生物共同栖息的水域中持续存在。